Tofacitinib treatment alters mucosal immunity and gut microbiota during experimental arthritis

Hablot, Julie; Ferhat, Maroua; Lavelle, Aonghus; Salem, Fatouma; Taieb, Mahdia; Medvedovic, Jasna; Kindt, Nadège; Reboul, Pascal; Cailotto, F.; Jouzeau, Jean‐Yves; Eberl, Gérard; Sokol, Harry; Moulin, David

doi:10.1002/ctm2.163

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…The role of gut microbiota in pathophysiology of alopecia areata has been suggested [ 48 ]. Recently, it was shown that JAK inhibitors affect gut microbiota [ 59 ]. The influence of JAK inhibitors on gut microbiota in patients with alopecia areata may result in hair regrowth but also causes gastrointestinal adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review

2023

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Background and Objectives Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata. Methods The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023. Results In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3). Conclusions The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-023-01260-z.

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Section: Discussionmentioning

confidence: 99%

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review

2023

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“…También empiezan a reportarse algunos datos del tofacitinib en la microbiota, en modelos de artritis, en los que se han valorado los efectos en la tejido linfoide asociado a mucosa y el aumento de poblaciones de firmicutes 20 .…”

Section: Efectos Sobre La Microbiota De Los Medicamentos Usados En La...unclassified

Eje intestino-cerebro-microbiota, ¿una vía para futuros tratamientos en la enfermedad inflamatoria intestinal?

San Vicente-Parada

2023

IMIDS

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“…In contrast, Hablot et al . reported that although tofacitinib was not associated with altered alpha diversity of the gut microbiota in a mouse model of rheumatoid arthritis from day 21 of treatment, it was associated with altered beta diversity [ 113 ] . In the treated mice, a reduction in potential pathogenic members of the phyla Proteobacteria and Chlamydiae was noted, along with an increase in some beneficial members of Actinobacteria and Firmicutes.…”

Section: Targeted Oral Synthetic Drugmentioning

confidence: 99%

Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches

O’Reilly,

Mills,

Rea

et al. 2023

Microbiome Res Rep

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Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a “healthier profile” and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.

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Tofacitinib treatment alters mucosal immunity and gut microbiota during experimental arthritis

Cited by 7 publications

References 6 publications

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review

Eje intestino-cerebro-microbiota, ¿una vía para futuros tratamientos en la enfermedad inflamatoria intestinal?

Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches

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